1. Field of the Invention
The present invention relates to a multi-block thermoplastic polyurethanes system, and, more specifically, to a system incorporating polyhedral oligomeric silsesquioxane into conventional biodegradable thermoplastic polyurethanes.
2. Description of the Related Art
Biostability is of critical importance for biomaterials applied for long-term medical implants. Thermoplastic polyurethanes (“TPUs”) are composed of hard segment and soft segment. The hard segment block consists of a selected diisocyanate and a selected chain extender. The soft segment is usually a polyol, either hydroxyl- or amine-terminated polyester, polyether, or polycarbonate. The flexible soft segment affords the TPUs great elasticity while the hard segment contributes strength. Both segments are incompatible and tend to form phase-separated morphology. Due to their great potential in tailoring polymer structures, polyurethanes have unique mechanical properties and good biocompatibility that make them ideal for many implantable biomedical devices, including artificial hearts components, heart valves, vascular grafts, and mammary prostheses. Since their introduction, many different polyurethanes have been evaluated for their stability in the biological environment using both in vitro and in vivo test procedures. It has been recognized that polyester-based polyurethanes are not suitable for long-term implantation due to their susceptibility to hydrolytic degradation.
Both poly(ε-caprolactone) (“PCL”) and poly(ethylene glycol) (“PEG”) are biocompatible and non-immunogenic. So far, there have been several PCL- and/or PEG-based biomedical products for various clinical uses approved by the U.S. Food and Drug Administration (“FDA”). Polycaprolactone is one of the most promising synthetic polymers that can degrade in contact with microorganisms. The related enzymatic hydrolytic degradation of PCL-based polymers has also been investigated, especially in the presence of ester-bond cleavage enzymes. Lipases are among the most popularly studied enzymes to catalyze the cleavage of ester bonds by transesterification. Importantly, semicrystalline PCL blocks make the associated polyurethanes stiff and hydrophobic, limiting its compatibility with soft tissues and the range of potential applications.
Poly(ethylene glycol) is one of the most widely studied synthetic polymers used for designing hydrogels in the biomedical applications. The intrinsic hydrophilicity of PEG-based hydrogels repels nonspecific protein adsorption and resists bacterial and animal cell adhesion. Its elastic and soft natures enable them to have low mechanical and frictional irritation when to contact with tissues and organs. However, PEG-based polyurethanes showed poor mechanical properties. The properties of these polymers can be improved by either blending or copolymerization. Because of the combination of great advantages of PCL and PEG, PCL-PEG-based copolymers might have great potential application in biomedical fields including drug delivery, cell encapsulation, and tissue engineering. A family of new biodegradable segmented polyurethanes with a wide variety of chemical and mechanical properties suitable for use in soft tissue applications has previously been developed. The hard segments of these materials are composed of a phenylalanine-based diester chain extender and a lysine-based diisocyanate. The soft segments are either a PCL or PEG diol. Through blending of PCL and PEG-based polyurethanes, the degradation rate and mechanical properties have been optimized. Due to its vulnerability to hydrolytic and oxidative degradation, PCL-PEG-based copolymers have proven unsuitable for long-term implantation.
Polyhedral oligosilsesquioxane (“POSS”) is a class of hybrid molecules with an inorganic silicon-oxygen cage (Si8O12) and eight variable organic side groups pendant to each silicon corner of the cage with the size of 1˜3 nm. The silica-like framework renders POSS cages chemically stable, non-toxic, and mechanically robust. Past work on POSS polyurethanes concerned microstructure-deformation studies, biodegradation, controlled drug delivery, and biocompatibility. In vitro hydrolysis and oxidation tests have been conducted in order to assess the degradative resistance of polyhedral oligosilsesquioxane integrated poly(carbonate-urea)urethane (POSS-PCU). These studies revealed that all samples showed no significant difference in their compliance and elasticity after a 70-day hydrolysis and oxidation test, indicating their striking biostability. Thus it was proposed that POSS nanocores covalently incorporated in PCU chains imparts a type of “protective” or “shielding effect” on the soft phase, thereby preserving its elasticity and compliant properties in oxidation and hydrolysis. Polycarbonate-urethane itself, however, possesses a greater biostability than does polyether-urethane and polyester-urethane. How to change polyether- and polyester-based urethanes from a biodegradable form to a biostable form by incorporation of POSS (or other means) has not yet been reported.